efinopegdutide (MK-6024) / Hanmi, Merck (MSD) - LARVOL DELTA

Efficacy and Safety of Incretin-Based Therapies in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Trials (ACG 2026) - "Agents included liraglutide, semaglutide, dulaglutide, tirzepatide, pemvidutide, survodutide, efinopegdutide, and retatrutide... Sixteen MASLD/MASH randomized trials were included. Five biopsy-based trials contributed to MASH/NASH resolution without worsening fibrosis (n=1,226); incretin-based therapy increased resolution versus control (RR 2.80, 95% CI 1.60â4.90; p=0.007; I²=66.6%). Four biopsy-based trials reported fibrosis improvement without MASH worsening (n=1,181), favoring incretin-based therapy (RR 1.52, 95% CI 1.13â2.05; p=0.021; I²=0%)."

Retrospective data • Review • Constipation • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Future GLP-1 receptor co-agonists and their cardiac effects. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Agonists at glucagon-like-peptide-1 receptors (GLP-1R) are becoming approved drugs to treat not only type 2 diabetes and obesity but also cardiac diseases such as coronary heart disease, myocardial infarction and heart failure...We discuss here the known (for tirzepatide and retatrutide) or predicted contractile effects of such co-agonists on isolated cardiac preparations of experimental animals, mainly in mice and compare these results with data in isolated human cardiac preparations...We will discuss not only receptor agonists but also a receptor antagonist (AMG133). We identify research needs and controversies in the literature. We make suggestions for further preclinical research and what improvements in drug design for treatment may lie ahead."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Myocardial Infarction • Obesity • Type 2 Diabetes Mellitus

A Clinical Study of Efinopegdutide in People With Compensated Cirrhosis Due to Steatohepatitis (MK-6024-017) (clinicaltrials.gov) - P2 | N=85 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review. (PubMed, Ann Intern Med) - "To update our prior systematic review evaluating the efficacy and safety of GLP-1 RAs and co-agonists among adults with overweight or obesity without diabetes...Among commercially available therapies, placebo-subtracted weight loss reached up to -5.8% (95% CI, -8.0% to -3.6%) for liraglutide, -14.8% (CI, -16.2% to -13.4%) for subcutaneous semaglutide, -14.3% (CI, -17.2% to -11.4%) for oral semaglutide, -12.4% (CI, -15.1% to -9.7%) for orforglipron, and -19.0% (CI, -21.6% to -16.4%) for tirzepatide. Numerically greater placebo-subtracted reductions were seen with emerging multiagonists, including -23.9% (CI, -29.3% to -18.5%) with amycretin and -22.1% (CI, -24.9% to -19.3%) with retatrutide...Head-to-head data showed greater weight loss with semaglutide and JNJ-64565111 than liraglutide and greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema; Novo Nordisk) than semaglutide...None. (PROSPERO: CRD42024505558)."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Defining the efficacy and tolerability ceiling of pure incretin therapies in steatotic liver disease: a network meta-analysis of phase 2 and 3 trials (EASD 2026) - "(1) Liver Fat Clearance (MRI-PDFF): The tri-agonist retatrutide achieved the highest efficacy hierarchy (SUCRA 98%), yielding a -82.4% relative reduction in hepatic steatosis. GLP-1/glucagon dual-agonists (mazdutide, efinopegdutide) consistently outperformed both GLP-1/GIP agents and pure GLP-1 mono-agonists...While earlier dual-agonists (survodutide, cotadutide) exhibited high adverse event-related discontinuation rates (15.2-20.0%), next-generation agents (mazdutide, pemvidutide) maintained placebo-like tolerability (<1.0% discontinuation) alongside profound hepatic fat clearance. Multi-receptor incretin agonism yields a stepwise, dose-and-receptor dependent superiority in clearing hepatic steatosis compared to pure GLP-1 therapy. While the addition of glucagon drives unparalleled fat clearance, optimizing the tolerability profile remains the defining factor for the clinical viability of next-generation incretins."

P2 data • Retrospective data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Evolution of incretin-based therapies: From GLP-1 monotherapy to dual and triple agonists: A new era in metabolic therapy. (PubMed, Indian J Med Res) - "While DPP-4 inhibitors offer modest glycaemic benefits, GLP1RAs such as liraglutide and semaglutide have demonstrated significant weight loss and cardiometabolic protection. Dual GIP/GLP-1 agonist tirzepatide and triple agonist retatrutide have shown unprecedented efficacy, with up to 24% body weight reduction and improvement in hepatic and inflammatory markers. Agents like cotadutide and efinopegdutide further expand indications to MASLD and metabolic dysfunction associated steatohepatitis (MASH)...Incretin-based multi-agonists offer a transformative, multi-system approach to metabolic disease but require tailored implementation. This review provides an updated synthesis of therapeutic developments and outlines priorities for future research, regulatory policy, and equitable global integration as incretin-based therapies have evolved into a versatile class addressing glycaemic control, weight loss, and cardio-metabolic risk."

Journal • Monotherapy • Review • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

…efinopegdutide, a treatment for metabolic dysfunction-associated steatohepatitis (MASH) led by partner U.S.-based Merck & Co. (MSD), completed its Phase 2b clinical trial in December last year, with results expected to be presented at a medical conference in the first half of this year. (Business Korea)

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

A Clinical Study of Efinopegdutide in Participants With Precirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-6024-013) (clinicaltrials.gov) - P2 | N=381 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Clinical Study of Efinopegdutide in People With Compensated Cirrhosis Due to Steatohepatitis (MK-6024-017) (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Alternate Dosing Study of MK-6024 in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (MK-6024-016) (clinicaltrials.gov) - P2 | N=124 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Clinical Study of Efinopegdutide in People With Compensated Cirrhosis Due to Steatohepatitis (MK-6024-017) (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: May 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis. (PubMed, J Clin Endocrinol Metab) - "GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • KRT18

Korean firms join competition for new liver disease treatments amid Rezafungin lead (Chosun Biz) - "Recently, Novo reported that 62.9% of patients in the Wegovy treatment group showed improvements in MASH symptoms without worsening liver fibrosis, and 37% showed improvements in liver fibrosis. The company plans to apply for FDA approval in the first half of this year based on these results....Hanmi Pharmaceutical...is conducting a joint phase 2b clinical trial comparing the efficacy of efinopegdutide and Wegovy with MSD in the United States, and is expected to announce results by the end of this year."

FDA filing • P2b data • Metabolic Dysfunction-Associated Steatohepatitis

A Study of Efinopegdutide in Healthy Obese Participants (MK-6024-015) (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Obesity

A Clinical Study of Efinopegdutide (MK-6024) in Healthy Chinese Volunteers (MK-6024-011) (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

Hanmi Pharmaceutical's 'Obesity Drug' Expected to Transfer Technology Overseas... Aiming for a Rebound [Google translation] (Money Today) - "'Efinopegdutide', a treatment for metabolic steatohepatitis (MASH) that was previously transferred to Merck (MSD), has also completed the recruitment of patients for phase 2b clinical trials, and the clinical trials are expected to be completed by the end of the year and the results are expected to be announced early next year....The company has brought forward the launch schedule of Efinopegdutide, which was originally set for 2027, to the fourth quarter of next year."

Enrollment closed • Launch • P2b data • Trial completion date • Metabolic Dysfunction-Associated Steatohepatitis

A Phase 1b Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of JNJ-64565111 in Participants With Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: Janssen Research & Development, LLC | Phase classification: P1b ➔ P1

Phase classification • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis. (PubMed, Cureus) - "Semaglutide, liraglutide, and efinopegdutide were well-tolerated and were associated with primarily minimal to moderate severity adverse effects, most of which were gastrointestinal. Future studies should continue to focus on conducting direct comparisons between GLP-1 RAs and emerging multi-receptor GLP-1 RAs, such as efinopegdutide, tirzepatide, and retratrutide, to determine clinical efficacy, long-term safety, and identifying the most effective regimens for clinical practice."

Journal • Retrospective data • Review • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study of Efinopegdutide in Participants With Hepatic Impairment (MK-6024-014) (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

A Study of Efinopegdutide in Participants With Hepatic Impairment (MK-6024-014) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

A Study of Efinopegdutide in Healthy Obese Participants (MK-6024-015) (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial • Obesity

Alternate Dosing Study of MK-6024 in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (MK-6024-016) (clinicaltrials.gov) - P2 | N=129 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Jun 2025 | Trial primary completion date: Oct 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

COMPARATIVE EFFICACY OF PHARMACOLOGIC THERAPIES FOR MASH IN REDUCING LIVER FAT CONTENT: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (AASLD 2024) - "By comparison of absolute MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were the most efficacious interventions. Efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were the most efficacious interventions for achieving ≥30% decline in MRI-PDFF at 24 weeks...Efruxifermin, aldafermin and pegozafermin were the most efficacious for MRI-PDFF decline at 12 weeks by both the absolute decline and achieving ≥30% decline in MRI-PDFF. At 48 weeks, Cilofexor + firsocostat, selonternib + firsocostat and cilofexor were most efficacious in absolute reduction in MRI-PDFF, while semglutide, tropifexor and tropifexor + cenicriviroc were most efficacious in achieving ≥30% decline in MRI-PDFF... This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat as assessed by MRI-PDFF. These data may help inform the design and..."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

THERAPEUTIC HORIZONS IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE(MASLD) & METABOLIC DYSFUNCTION ASSOCIATED STEATOHEPATITIS(MASH): A SYSTEMATIC REVIEW OF CURRENT TREATMENT OPTION (AASLD 2024) - " Study results are comprehensively mentioned in Table 1 with key findings summarized as below: GLP-1 agonists: Analyzing 13 trials with 1,476 patients, Semaglutide reduced liver fat by 73% (P<0.05), and other agonists like Liraglutide and Efinopegdutide also significantly decreased liver fat and improved fibrosis markers (P<0.001); Lifestyle interventions: 12 trials with 1,032 patients showed significant liver marker improvements with the Mediterranean diet(P<0.001), calorie restriction with pentadecanoic acid(P<0.001), intermittent fasting with exercise (P<0.05), and technology-assisted interventions (P<0.001); Berberine: 4 trials with 415 patients demonstrated Berberine's effectiveness in reducing liver fat and improving LFTs (P<0.05), especially at higher doses and in combination with Ursodeoxycholic acid. Our SR shows that GLP-1 agonists are effective on liver fat reduction.Bariatric surgery is highly effective for MASLD and MASH but..."

Review • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Alternate Dosing Study of MK-6024 in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (MK-6024-016) (clinicaltrials.gov) - P2 | N=105 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease